ABSTRACT
Sorafenib is considered a standard of care in advanced hepatocellular carcinoma [HCC]. Its combination with gemcitabine, a pyrimidine analogue with limited friendly hepatic profile may prove beneficial in advanced HCC. The primary objective was to evaluate the efficacy and safety of a sorafenib and gemcitabine combination in patients with advanced HCC. This was a non-randomized, open-label, single-arm, multi-centric Phase II study conducted in Pakistan where 30 treatment-naive patients aged between 26 and 73 years with Child-Pugh score A or B were treated with sorafenib [400 mg oral] twice daily for 16 weeks along with gemcitabine [1000 mg/m[2] intravenous] administered on day 1 and day 8 of a four-week cycle for 16 weeks. Of the 18 patients [60%] who completed all four cycles of treatment, eight patients had stable disease, two had partial response, and eight had progressive disease. There was no complete response. The most common [>/= 10% patients] treatment-emergent adverse events were gemcitabine-related thrombocytopenia [40%] followed by sorafenib-related hand-foot skin reaction and anorexia [33% each]. The efficacy of sorafenib gemcitabine combination therapy is similar to the sorafenib alone treatment. However, frequent dose adjustments due to gemcitabine-related toxicities, delays, and corrective treatments make this combination therapy unsafe in the treatment of advanced HCC.
ABSTRACT
To determine the efficacy and toxicity of Gemcitabine, Vinorelbine and Prednisolone [GVP] salvage chemotherapy in relapsed / refractory Hodgkin's Lymphoma [HL]. A phase-II non-randomized single arm study. This study was conducted at Combined Military Hospital and Medical College Lahore, Mayo Hospital, King Edward Medical University, Lahore, Allied Hospital, Punjab Medical College, Faisalabad and Combined Military Hospital, Rawalpindi, from January 2007 to December 2007. Fifty adult patients with relapsed/refractory HL, adequate marrow reserve, hepatorenal and pulmonary functions, with radiological measurable disease and Karnofsky performance status of 0 - 2 non-candidates for stem cell transplantation, were enrolled. Four 28 days cycles of GVP [Gemcitabine 1000 mg/m2, Vinorelbine 30 mg/m2 on day 1 and 8 intravenously with oral Prednisolone 100 mg/day on day 1 - 5] were given. Response evaluation done according to Cotswolds meeting recommendations and toxicity was evaluated with NCI-CTC [National Cancer Institute - Common Terminology Criteria for adverse events v 3.0]. Forty patients completing 4 cycles of GVP, 14 refractory/early relapse and 26 late relapsed [one year postprimary treatment with ABVD] were available for evaluation. The overall response [CRu+PR] rate was 77.5% with better response 85% in late relapsed patients. Haematological toxicity was most common and seen in 70% of cases. GVP is well-tolerated regimen with high response rate and needs to be tested in late relapsed H